1. Field of the Invention
The invention relates to the field of biomarkers which are diagnostic or prognostic for predicting patient response to specific anti-cancer compounds and therapeutics.
2. Background
The pharmaceutical industry estimates that there are more than 800 small molecule agents and biologics now under development for treatment of human malignancies (website for newmeds.phrma.org). These agents target numerous molecular features thought to distinguish between tumor and normal cells. These range from broad specificity conventional therapeutics such as anti-metabolites and DNA crosslinking agents that currently serve as mainline breast cancer treatments, to agents that interfere with aspects to a new generation of agents such as trastuzumab that selectively target molecular events and pathways that are deregulated in cancer subsets.
The general trend in drug development today is toward development of more targeted agents because these are expected to show increased efficacy and lower toxicity than conventional agents. Some drugs such as the ERBB2/EGFR inhibitor, lapatinib show high target specificity while others such as the SRC inhibitor, dasatinib, inhibit a broad range of kinases. Given the large number of agents in clinical development, there is growing recognition that clinical trials must include predictors of response and must stratify patients entering the trial.
Unfortunately, the specificity of most drugs is not sufficiently high to allow the subtypes in which the drugs will be effective to be predicted with high confidence. Responsive subsets can be identified during the course of molecular marker based clinical trials however this is logistically difficult, expensive and does not allow experimental compounds to be tested in subpopulations most likely to respond early in the trials process. Indeed, the majority of drugs now under development will never be tested in breast cancer so the probability is high that compounds that are effective only in subpopulations of breast cancer will be missed.